Method for the n-alkylation of phenylaminoacetic acid esters



Patented Jan. 5, 1954 METHOD FOR THE N-ALKYLATI ON OF PHENYLAMINOACETIC ACID ESTERS Norbert Brock, .Brackvve Gadderbaum, and Mai- Germany, assignors 'ges'ellschaft, Chemise Westphalia, Germany as, sli htrt *Kiihiis, tin Schmeisser, Munich,

to Asta-Werke Aktienhe Fabrik, 'Brackw''de,

No Drawing. Application January 23, 1951, Serial No. 207,446

Claims priority, application Austria January 25, 1950 4 Claims.

It is well known that compounds having aromatically bonded amino groups can be converted into the corresponding N-alkyl compounds by the action of dialkylaminoalkylchlorides. This reaction is generally carried out using the dialkylaminoalkylchloride in the form of a free base in the presence of neutral solvents. There is no information regarding the yield produced by this reaction.

As far as we are aware N-alkylations of phenylaminoacetic acid esters have not been carried out. Attempts to obtain the N-alkylation of phenylamino-acetic acid esters by the abovementioned usual method, that is, by using the free base in the presence of neutral solvents have given very poor yields, in general not more than 20%.

On the other hand it has been discovered that surprisingly high yields of N-alkylation products are obtained in the N-alkylation of phenylaminoacetic acid esters, provided that the reaction is carried out in the absence of solvents with the aid of the hydrochloride of the dialkylami noalkylchloride base. Under these conditions yields of 80% or more are obtained. It has been found that particularly good results are obtained if phenylaminoacetic acid iso-amylester is reacted, for example, with diethylaminoethylchloride hydrochloride in the absence of solvents. In this manner on the one hand, particularly high yields (over 80%) are obtained, while on the other hand, compounds are obtained which exhibit extremely valuable therapeutical properties.

Examples ish translucent mass follows:

The reaction product is dissolved in water, made alkaline and then ether is added. After drying the etheric solution with sodium sulphate, the ether is removed and the residue is fractionally distilled in vacuo. After slight forerunnings, the ester distils over at B. P4 165 to 180. Yield 58 g.=80.11%.

The compound obtained by the N-alkylation of phenylaminoacetic acid iso-amyl ester is characterised in the form of its hydrochloride by excellent cramp-relieving action. It is in particular suitable for the treatment of spasms due to muscular or neural causes.

Since the hydrochloride of dialkylaminoethyl chloride, unlike the free base, is quite stable, it can be stored without any trouble and can be using the free base where the base used must be prepared from the hydrochloride with a considerable loss, and the base on account of its sensitivity and instability must be specially prepared from the hydrochloride for each operation.

Occasionally N-alkylations of compounds containing aromatically bonded amino radicals and not belonging to the series of the phenylaminoaceticacid esters have also been carried out by using, instead of the free dialkylaminochloride base, the corresponding hydrochloride and by treating without solvents. There is however no data at hand to show that better yields are obtained than by the usual process using the free base. Therefore no conclusions could be drawn that in the N-alkylation of phenylamino acetic which may be treated as acid esters using the hydrochloride in the absence of solvents, yields could be obtained which are a multiple of, for example, four times the yield which is obtained by using the free base in the presence of solvents. It could not be foreseen either, that compounds according to the invention would be obtained with high yields, for example 80% or more, having special therapeutic properties in particular cramp-relieving actions as for example those exhibited by the N alkylation products of phenylaminoacetic acid iso-amyl ester, in the form of their hydrochlorides.

We claim: 1. As a novel therapeutically useful compound,

the isoamylester of alpha- (N' diethylamino- 5 C2115 CiH5 wherein R stands for the isoamyl radical.

2. As a novel therapeutically useful compound the hydrochloride of the isoamylester of alpha- (N' diethylaminoethyl N amino) phenylacetic acid.

3. A method for producing the isoamylester of alpha (N' diethylaminoethyl N amino)- phenylacetic acid which comprises reacting alpha 4 phenylaminoacetic acid isoamyl ester in the absence of solvents with diethylaminoethyl-chloride hydrochloride.

4. A method for producing the isoamylester of alpha (N dimethylaminoethyl N amino) phenylacetic acid which comprises reacting alpha phenylaminoacetic acid isoamylester in the absence of solvents with dimethylaminoethylchloride hydrochloride.

NORBERT BROCK. ENGELBERT KiiHAs. MARTIN SCHMEISSER.

References Cited in the file of this patent UNITED STATES PATENTS Number 1 H Name Date 1,958,469 Christmann et a1. May 15, 1934 2,176,441 Ulrich et a1. Oct. 17, 1939 20 2,230,774 Bockmeuhl et a1. Feb. 4, 1941 2,293,034 Moore Aug. 18, 1942 2,470,094 Dickey et a1 May 17, 1949 

1. AS A NOVEL THERAPEUTICALLY USEFUL COMPOUND, THE ISOAMYLESTER OF ALPHA - (N''-DIETHYLAMINOETHYL-N-AMINO) -PHENYLACETIC ACID OF THE FORMULA 